The pathophysiology of pulmonary hypertension (PH) is not fully understood. Here, we tested the hypothesis that hypoxic perfusion of the vasa vasorum of the pulmonary arterial (PA) wall causes PH. Young adult pig lungs were explanted and placed into a modified ex vivo lung perfusion unit (Organ care system, OCS) allowing the separate adjustment of parameters for mechanical ventilation, as well as PA perfusion and bronchial arterial (BA) perfusion. PA vasa vasorum are branches of the BA. The lungs were used either as control (n=3) or intervention group (n=8). The protocol of the intervention group was as follows: normoxic ventilation and perfusion (steady state) -hypoxic BA perfusion -steady state -hypoxic BA perfusion. During hypoxic BA perfusion, ventilation and PA perfusion maintained normal. Control lungs were kept under steady state conditions for 105 minutes. During the experiments, PA pressure (PAP) and blood gas analysis was frequently monitored. Hypoxic perfusion of the BA resulted in an increase in systolic and mean PAP, a reaction that was reversible upon normoxic BA perfusion. The PAP increase was reproducible in the second hypoxic BA perfusion. Under control conditions the PAP stayed constant until about 80 minutes of the experiment. In conclusion, the results of the current study prove that hypoxic perfusion of the vasa vasorum of the PA directly increases PAP in an ex situ lung perfusion setup suggesting that PA vasa vasorum function and wall ischemia may contribute to the development of PH.
Keywords: ex vivo lung perfusion; hypoxia; pulmonary artery; pulmonary hypertension; vasa vasorum.